Evaluation of Cortical Resonant Oscillations as a Novel Target for Treatment of Dyskinesia

Dyskinesia Challenge, 2012

Objective/Rationale: In our research we aim to identify changes in neuronal circuits that cause motor symptoms in Parkinson’s disease (PD) by recording neuronal activity in healthy and in parkinsonian pre-clinical models. We recently discovered that when parkinsonian models experience levodopa-induced dyskinesia this is always associated with high-frequency oscillations in motor areas of the cerebral cortex. We hypothesize that when these oscillations are blocked by certain pharmacological substances, dyskinetic symptoms are alleviated.

Project Description: We will now further investigate how this physiological phenomenon is linked to dyskinetic symptoms and evaluate different strategies to interfere with the oscillation in order to reduce levodopa-induced dyskinesia. Because activity in one part of the brain often affects other interconnected structures, we also will investigate to what extent this aberrant pattern can been found in deeper parts of the brain known to be affected in PD.

Relevance to Diagnosis/Treatment of Parkinson’s Disease: Understanding more about the mechanisms that cause motor symptoms with levodopa treatment of PD is an important first step towards improved treatment strategies.

Anticipated Outcome: We believe this research will lead to a better understanding of the physiological mechanisms causing levodopa-induced dyskinesia and may suggest novel future targets for symptomatic treatment.

FINAL OUTCOME

In this study we have used parkinsonian models to investigate which specific activity patterns in different brain structures are strongest associated with dyskinetic symptoms induced by levodopa treatment. After having identified these brain activity patterns, we evaluated if pharmacological interventions aimed at changing the activity back to a more normal state could guide us in how to more effectively alleviate dyskinetic symptoms. We also tested to what extent electrical stimulation of specific regions in the brain could have a similar beneficial effect by interfering with the identified aberrant activity patterns. The results of our studies support the notion that dyskinesia is strongly associated with specific oscillatory patterns in certain brain regions and that interventions that are effective in interfering with these oscillations are beneficial with regard to alleviation of levodopa-induced dyskinesia. These findings will likely be very helpful in the future development of novel ways to treat dyskinesia.